Fibromyalgia (FM) is a syndrome of unknown cause and poorly understood pathophysiology. It has been estimated to have a prevalence rate of up to 10% in some populations. Previous studies have suggested that the fatigue and muscle pain associated with this syndrome can be correlated with anatomic and physiologic changes in skeletal muscle. We propose to apply the techniques of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) to the study of patients with FM. In previous investigations, we have shown that the fatigue associated with other musculoskeletal syndromes, such as amyopathic dermatomyositis, may be explained by changes in the biochemical and physiological responses of muscle. We propose to apply these techniques to the study of patients with FM, with three specific aims. First, a cross-sectional study of 20 to 25 FM patients will be carried out using our previously reported MR and P-31 MRS protocols for: (l) MR images of thigh muscles acquired with a Carr- Purcell-Meiboom-Gill sequence to visualize abnormalities and calculate T1 and T2 values and (2) P-31 MR spectra to determine levels of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters and phosphodiesters during rest, graded exercise and recovery. These data will be compared to ongoing and previous results in patients with inflammatory myopathies, and to age- and sex-matched normal controls. Second, 10 of these individuals will have more intensive studies using (A) localized spectroscopy of areas of muscle adjacent to painful trigger points, to include direct measurement of P-31 metabolites and intracellular concentrations of lactic acid and creatine, and (B) imaging and spectroscopy of the upper extremities. The third aim will be to study 10 to 12 newly diagnosed FM patients who are beginning standard treatment with tricyclic medications and/or physical therapy. These patients will be followed longitudinally for up to 18 months. Findings will be correlated with responses of each patient on self-assessment questionnaires covering daily activities, work-related activities and more vigorous recreational exercise. With the use of these sensitive techniques, we expect to be able to determine definitively whether or not anatomic or biochemical abnormalities of muscle are associated with FM. These data in turn may suggest new approaches to diagnosis and treatment of this disorder.